Substances Included Synonyms

Therapeutic Toxic Class

A)

Specific Substances

1) 2-(2-butoxyethanoxy) ethanol
2) Butoxydiethylene glycol
3) Butyl carbitol
4) Butyl digol
5) DGBE (diethylene glycol butyl ether)
6) Diethylene glycol monobutyl ether
7) Diglycol monobutyl ether
8) Molecular Formula: C8-H18-O3
9) CAS 112-34-5
10) BUCB
11) BUTYL DIOXITOL
12) ETHANOL, BUTOXYETHOXY

1.2.1) MOLECULAR FORMULA
1) C8-H18-O3

Available Forms Sources

A)

1) It is primarily used as a solvent in hard-surface cleaners and inks, and as a solvent and coalescing agent in paints and other coatings (Clayton & Clayton, 1994), as well as a melting-out solution in the textile industry or as a solvent for cellulose nitrate.

Overview

Life Support

A)

Clinical Effects

0.2.1)

A) USES: Butoxyethoxy ethanol or diethylene glycol monobutyl ether (DGBE) is a colorless, odorless liquid. It is primarily used as a solvent in hard-surface cleaners and inks, and as a solvent and coalescing agent in paints and other coatings. It is also used as a melting-out solution in the textile industry or as a solvent for cellulose nitrate.
B) TOXICOLOGY: DGBE has a low order of toxicity via the oral, dermal and inhalational route. The primary urinary metabolites are 2-butoxyethoxyacetic acid, along with diethylene glycol, and hydroxybutoxyethoxyacetic acid.
C) EPIDEMIOLOGY: Acute poisoning is relatively rare but DGBE is used widely in industrial settings and chronic exposure may occur in many workers among certain industries.
D) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: DGBE is an irritant to eyes, skin, and mucosa. Increased intraocular pressure was noted after instillation of a 0.4 mL of a 10% solution of DGBE. Patients may experience nausea, vomiting, and diarrhea following ingestion of DGBE.
2) SEVERE TOXICITY: Tachypnea, cyanosis, uremia and impaired kidney function have been observed. Large and intentional exposures to other diglycol ethers have resulted in reports of CNS depression, metabolic acidosis, renal injury, and acute lung injury. Theoretically, acidosis may occur.

0.2.20)

A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

0.2.21)

A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

A)

B)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) Treatment is predominantly decontamination, and symptomatic and supportive care. Monitor patients for respiratory distress.

B) MANAGEMENT OF SEVERE TOXICITY

1) In patients with severe toxicity, supportive care with attention to monitoring for respiratory depression is recommended. Following an inhalational exposure, move the patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists and systemic corticosteroids if bronchospasm develops. Acid-base balance should be assessed after significant ingestion or in symptomatic patients. Monitor and support renal function. There is no data to evaluate the efficacy of alcohol dehydrogenase inhibition with ethanol or fomepizole; it should be considered in patients who develop significant metabolic acidosis or acute renal failure.

C) DECONTAMINATION

1) PREHOSPITAL: Gastrointestinal decontamination is not recommended after ingestion because of the risk of CNS and respiratory depression and aspiration. Remove contaminated clothing and wash exposed area thoroughly with soap and water. Irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If present, carefully remove contact lenses.
2) HOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway. However, given the low order of toxicity of this compound, routine administration of activated charcoal is not recommended. Remove contaminated clothing and wash exposed area thoroughly with soap and water. Irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If present, carefully remove contact lenses. If irritation, pain, swelling, lacrimation, or photophobia persists after 15 minutes of irrigation, an ophthalmologic examination should be performed.

D) AIRWAY MANAGEMENT

1) Administer 100% humidified supplemental oxygen; perform endotracheal intubation and provide assisted ventilation as required based on clinical signs. Administer inhaled beta2-adrenergic agonists and systemic corticosteroids if bronchospasm develops.

E) ANTIDOTE

1) There is no specific antidote for treatment of DGBE exposure. At the time of this review, there are insufficient data to recommend the administration of an alcohol dehydrogenase inhibitor (fomepizole or ethanol). However, this is reasonable in a patient who develops metabolic acidosis following DGBE exposure. FOMEPIZOLE VS ETHANOL : Fomepizole is easier to use clinically, requires less monitoring, and does not cause CNS depression or hypoglycemia. Ethanol requires continuous administration and frequent monitoring of serum ethanol and glucose levels, and may cause CNS depression and hypoglycemia (especially in children). The drug cost associated with ethanol use is generally much lower than with fomepizole; however, other costs associated with ethanol use (continuous intravenous infusion, hourly blood draws and ethanol levels, possibly greater use of hemodialysis) may make the costs more comparable.

a) FOMEPIZOLE: Fomepizole is administered as a 15 mg/kg loading dose, followed by four bolus doses of 10 mg/kg every 12 hours. If therapy is needed beyond this 48 hour period, the dose is then increased to 15 mg/kg every 12 hours for as long as necessary. Fomepizole is also effectively removed by hemodialysis; therefore, doses should be repeated following each round of hemodialysis.
b) ETHANOL: Ethanol is given to maintain a serum ethanol concentration of 100 to 150 mg/dL. This can be accomplished by using a 5% to 10% ethanol solution administered IV through a central line. Intravenous therapy dosing, which is preferred, is 0.8 g/kg as a loading dose (8 mL/kg of 10% ethanol) administered over 20 to 60 minutes as tolerated, followed by an infusion rate of 80 to 150 mg/kg/hr (for 10% ethanol, 0.8 to 1.3 mL/kg/hr for a nondrinker; 1.5 mL/kg/hr for a chronic alcoholic). During hemodialysis, either add ethanol to the dialysate to achieve 100 mg/dL concentration or increase the rate of infusion during dialysis (for 10% ethanol, 2.5 to 3.5 mL/kg/hr). Blood ethanol concentrations must be monitored hourly and the infusion adjusted accordingly.

F) ENHANCED ELIMINATION PROCEDURE

1) There is no human data to evaluate the efficacy of enhanced elimination techniques. Hemodialysis may be considered in patients with severe metabolic acidosis or acute renal failure.

G) PATIENT DISPOSITION

1) HOME CRITERIA: Asymptomatic patients with inadvertent small exposures can be monitored at home.
2) OBSERVATION CRITERIA: Symptomatic patients or patients with known large exposure should be observed for 6 hours for signs of toxicity.
3) ADMISSION CRITERIA: Patients with significant symptoms should be admitted for treatment and monitoring. Patients with respiratory failure should be admitted to an ICU setting.
4) CONSULT CRITERIA: Consult a medical toxicologist or your regional poison center for any patients with severe toxicity. For patients with eye exposure, consult an ophthalmologist for assistance with ophthalmic examination if needed.

H) PITFALLS

1) Failure to detect airway compromise and lack of proper airway management. Failure to recognize progression and worsening of symptoms. Failure to detect/recognize acidosis and acute renal injury.

I) TOXICOKINETICS

1) DGBE has a low order of toxicity via the oral, dermal and inhalation. The most likely route of exposure is by the dermal route based on its extensive use in cleaning products and coatings. The primary urinary metabolites are 2-butoxyethoxyacetic acid, along with diethylene glycol, and hydroxybutoxyethoxyacetic acid. Two other unknown metabolites were also found. Following oral administration, it is anticipated that DGBE is primarily excreted (85% of dose) in the urine.

J) DIFFERENTIAL DIAGNOSIS

1) Ethylene glycol or methanol toxicity, diethylene glycol toxicity, salicylate toxicity, chlorine gas exposure, ammonia gas exposure, and irritant exposure.

0.4.3)

A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

A)

Clinical Effects

Summary Of Exposure

A)

B)

C)

D)

1) MILD TO MODERATE TOXICITY: DGBE is an irritant to eyes, skin, and mucosa. Increased intraocular pressure was noted after instillation of a 0.4 mL of a 10% solution of DGBE. Patients may experience nausea, vomiting, and diarrhea following ingestion of DGBE.
2) SEVERE TOXICITY: Tachypnea, cyanosis, uremia and impaired kidney function have been observed. Large and intentional exposures to other diglycol ethers have resulted in reports of CNS depression, metabolic acidosis, renal injury, and acute lung injury. Theoretically, acidosis may occur.

Vital Signs

3.3.2)

A) WITH POISONING/EXPOSURE

1) TACHYPNEA was reported following a human ingestion of 2 mL/kg (Brennaas, 1960).

Heent

3.4.3)

A) WITH POISONING/EXPOSURE

1) SUMMARY: It is moderately irritating to the eyes. Instillation may increase intraocular pressure.
2) CONJUNCTIVITIS and transient corneal injury may be seen (Ballantyne, 1984; Carpenter & Smyth, 1946).
3) INTRAOCULAR PRESSURE: Increased intraocular pressure was noted after instillation of a 0.4 mL of a 10% solution of diethylene glycol monobutyl ether (Ballantyne, 1984).

Respiratory

3.6.2)

A) HYPERVENTILATION

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Tachypnea was associated with cyanosis in one reported case (Brennaas, 1960).

Genitourinary

3.10.2)

A) UREMIA

1) WITH POISONING/EXPOSURE

a) Reduced kidney function and slight uremia may occur (Brennaas, 1960).

Acid-Base

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Since other diglycol ethers may cause acidosis, acid-base balance should be assessed in symptomatic patients.
b) LACK OF EFFECT: Brennaas (1960) did not report acidosis following an exposure (Brennaas, 1960).

Dermatologic

3.14.2)

A) SKIN IRRITATION

1) WITH POISONING/EXPOSURE

a) Irritation of the skin can be produced by DGBE (Clayton & Clayton, 1994). It usually occurs only after prolonged contact with the skin in large quantities (HSDB , 2000).

B) DISORDER OF SKIN

1) WITH POISONING/EXPOSURE

a) PERCUTANEOUS ABSORPTION: Dugard et al (1984) reported diethylene glycols are less rapidly absorbed through human epidermis than the corresponding monoethylene glycols (Dugard et al, 1984).

Reproductive

3.20.1)

A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

3.20.2)

A) LACK OF INFORMATION

1) At the time of this review, no data were available to assess the teratogenic potential of this agent.

3.20.3)

A) LACK OF INFORMATION

1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

B) ANIMAL STUDIES

1) Nolan et al (1985) reported no evidence of DGBE affect on fertility or embryonic development in rats and rabbits.

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS112-34-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

3.21.3)

A) LACK OF INFORMATION

1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Monitor pulse oximetry and/or arterial blood gases, chest radiograph and pulmonary function tests in patients with respiratory signs/symptoms.
B) In severe toxic cases, monitor renal function and evaluate for acidosis.

4.1.2)

A) ACID/BASE

1) Monitor pulse oximetry and/or arterial blood gases, chest radiograph and pulmonary function tests in patients with respiratory signs/symptoms.

B) BLOOD/SERUM CHEMISTRY

1) In severe toxic cases, monitor renal function and evaluate for acidosis.

4.1.3)

A) URINALYSIS

1) Obtain urinalysis following a significant exposure.

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Patients with significant symptoms should be admitted for treatment and monitoring. Patients with respiratory failure should be admitted to an ICU setting.

6.3.1.2) HOME CRITERIA/ORAL

A) Asymptomatic patients with inadvertent small exposures can be monitored at home.

6.3.1.3) CONSULT CRITERIA/ORAL

A) Consult a medical toxicologist or your regional poison center for any patients with severe toxicity. For patients with eye exposure, consult an ophthalmologist for assistance with ophthalmic examination if needed.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Symptomatic patients or patients with known large exposure should be observed for 6 hours for signs of toxicity.

Monitoring

A)

B)

Oral Exposure

6.5.1)

A) Gastrointestinal decontamination is not recommended after ingestion because of the risk of CNS and respiratory depression and aspiration. Remove contaminated clothing and wash exposed area thoroughly with soap and water. Irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If present, carefully remove contact lenses.

6.5.2)

A) SUMMARY: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway. However, given the low order of toxicity of this compound, routine administration of activated charcoal is not recommended.
B) ACTIVATED CHARCOAL

1) CHARCOAL ADMINISTRATION

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

2) CHARCOAL DOSE

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).

1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).

b) ADVERSE EFFECTS/CONTRAINDICATIONS

1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).

6.5.3)

A) SUPPORT

1) MANAGEMENT OF MILD TO MODERATE TOXICITY

a) Treatment is predominantly decontamination, and symptomatic and supportive care. Monitor patients for respiratory distress.

2) MANAGEMENT OF SEVERE TOXICITY

a) In patients with severe toxicity, supportive care with attention to monitoring for respiratory depression is recommended. Following an inhalational exposure, move the patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists and systemic corticosteroids if bronchospasm develops. Acid-base balance should be assessed after significant ingestion or in symptomatic patients. Monitor and support renal function. There is no data to evaluate the efficacy of alcohol dehydrogenase inhibition with ethanol or fomepizole; it should be considered in patients who develop significant metabolic acidosis or acute renal failure.

B) MONITORING OF PATIENT

1) Monitor pulse oximetry and/or arterial blood gases, chest radiograph and pulmonary function tests in patients with respiratory signs/symptoms.
2) In severe toxic cases, monitor renal function and evaluate for acidosis.

C) ACIDOSIS

1) METABOLIC ACIDOSIS: Treat severe metabolic acidosis (pH less than 7.1) with sodium bicarbonate, 1 to 2 mEq/kg is a reasonable starting dose(Kraut & Madias, 2010). Monitor serum electrolytes and arterial or venous blood gases to guide further therapy.

D) FOMEPIZOLE

1) SUMMARY: There is no specific antidote for treatment of DGBE exposure. At the time of this review, there are insufficient data to recommend the administration of an alcohol dehydrogenase inhibitor (fomepizole or ethanol). However, this is reasonable in a patient who develops metabolic acidosis following DGBE exposure.
2) Fomepizole, a specific antagonist of alcohol dehydrogenase, has been demonstrated to be highly effective in the treatment of ethylene glycol poisoning (Battistella, 2002; Druteika et al, 2002; Sivilotti et al, 2000; Borron et al, 1999; Brent et al, 1999).
3) Fomepizole has not been approved for use in children.
4) AVAILABILITY

a) Fomepizole is available in the United States for the treatment of methanol and ethylene glycol poisoning (Prod Info ANTIZOL(R) IV injection, 2006).

5) DOSE

a) An initial loading dose of 15 mg/kg is intravenously infused over 30 minutes followed by doses of 10 mg/kg/every 12 hours for 4 doses, then 15 mg/kg every 12 hours until ethylene glycol concentrations are below 20 mg/dL (Prod Info ANTIZOL(R) IV injection, 2006).
b) HEMODIALYSIS - The frequency of dosing should be increased during dialysis. If dialysis is begun 6 hours or more since the last fomepizole dose the next scheduled dose should be administered. Dosing during dialysis should be increased to every 4 hours (Prod Info ANTIZOL(R) IV injection, 2006).

1) If the last fomepizole dose was administered one to three hours before completion of dialysis, half of the next scheduled dose should be administered at the completion of dialysis. If the last fomepizole dose was administered more than 3 hours before completion of hemodialysis, the next scheduled dose should be administered when dialysis is completed.

6) ADVERSE EFFECTS

a) Studies in normal human volunteers show less side effects and slower elimination rate compared to ethanol (McMartin & Heath, 1989).
b) The manufacturer reported the most frequent adverse effects in 78 patients and 63 normal volunteers receiving fomepizole to be headache (14%), nausea (11%), and dizziness, increased drowsiness, and bad taste (6% each) (Prod Info ANTIZOL(R) IV injection, 2006).
c) A placebo-controlled, double-blind, multiple dose, sequential, ascending dose study among HEALTHY volunteers showed mild, transient increase in liver function tests and slower elimination rate of fomepizole (4-methylpyrazole). The mild, sporadic, and transient elevations in blood pressure were not dose-related (Jacobsen et al, 1990).

E) ETHANOL

1) EFFICACY

a) SUMMARY: There is no specific antidote for treatment of DGBE exposure. At the time of this review, there are insufficient data to recommend the administration of an alcohol dehydrogenase inhibitor (fomepizole or ethanol). However, this is reasonable in a patient who develops metabolic acidosis following DGBE exposure.
b) The role of ethanol therapy in preventing toxicity of glycol monoalkyl ethers is uncertain. Putative evidence suggests that ethanol therapy is beneficial. No human studies evaluating efficacy in poisoned patients are available. The parent ether compound is relatively nontoxic compared to the acetic acid metabolite. It is predicted that glycol ether toxicity may be reduced by blocking the production of the toxic metabolite by competitive inhibition of alcohol dehydrogenase with ethanol (Browning & Curry, 1994).
c) The presence of acid metabolites in animals and in vitro studies showing the ethyl and methyl ether to be a substrate for alcohol dehydrogenase (ADH) would indicate a potential for therapeutic effect of ethanol (Blair & Vallee, 1966).

2) INDICATIONS

a) Anion gap metabolic acidosis associated with a history of glycol ether ingestion
b) Any symptomatic patient with a history of glycol ether ingestion
c) A good history of substantial glycol ether ingestion
d) Keep in mind that glycol ether serum levels are not routinely available, and interpretation of such levels is difficult since a toxic range is not established. Thus, the endpoint of ethanol therapy will often be arbitrary.

3) AVAILABILITY

a) CONCENTRATIONS AVAILABLE (V/V)

1) In the United States, 5% or 10% (V/V) ethanol in 5% dextrose for intravenous infusion is no longer available commercially (Howland, 2011). Ethanol 10% (V/V) contains approximately 0.08 gram ethanol/mL.
2) ABSOLUTE ETHANOL or dehydrated ethanol, USP contains no less than 99.5% volume/volume or 99.2% weight/weight of ethanol with a specific gravity of not more than 0.7964 at 15.56 degrees C. Absolute ethanol is hygroscopic (absorbs water from the atmosphere) and when exposed to air may be less than 99.5% ethanol by volume (S Sweetman , 2002).

b) PREPARATION OF 10% V/V ETHANOL IN A 5% DEXTROSE SOLUTION

1) A 10% (V/V) solution can be prepared by the following method (Howland, 2011):

a) If available, use sterile ethanol USP (absolute ethanol). Add 55 mL of the absolute ethanol to 500 mL of 5% dextrose in water for infusion. This yields a total volume of 555 mL. This produces an approximate solution of 10% ethanol in 5% dextrose for intravenous infusion (Howland, 2011).

4) PRECAUTIONS

a) HYPOGLYCEMIA

1) Hypoglycemia may occur, especially in children. Monitor blood glucose frequently (Howland, 2011; Barceloux et al, 2002).

b) CONCURRENT ETHANOL

1) If the patient concurrently has ingested ethanol, then the ethanol loading dose must be modified so that the blood ethanol level does not exceed 100 to 150 mg/dL (Barceloux et al, 2002).

c) DISULFIRAM

1) Fomepizole is preferred as an alcohol dehydrogenase inhibitor in patients taking disulfiram. If fomepizole is not available, ethanol therapy should be initiated in those patients with signs or symptoms of severe poisoning (acidemia, toxic blood level) despite a history of recent disulfiram (Antabuse(R)) ingestion.
2) The risk of not treating these patients is excessive, especially if hemodialysis is not immediately available.
3) Administer the ethanol cautiously with special attention to the severity of the "Antabuse reaction" (flushing, sweating, severe hypotension, and cardiac dysrhythmias).
4) Be prepared to treat hypotension with fluids and pressor agents (norepinephrine or dopamine). Monitor ECG and vital signs carefully. Hemodialysis should be performed as soon as adequate vital signs are established, and every effort should be made to obtain fomepizole.

5) LOADING DOSE

a) INTRAVENOUS LOADING DOSE

1) Ethanol is given to maintain a patient’s serum ethanol concentration at 100 to 150 mg/dL. This can be accomplished by using a 5% or 10% ethanol solution administered intravenously through a central line (10% ethanol is generally preferred due to the large volumes required for 5%). Intravenous therapy dosing, which is preferred, is 0.8 g/kg as a loading dose (8 mL/kg of 10% ethanol) administered over 20 to 60 minutes as tolerated. Begin the maintenance infusion as soon as the loading dose is infused (Howland, 2011).

b) ORAL LOADING DOSE

1) Oral ethanol may be used as a temporizing measure until intravenous ethanol or fomepizole can be obtained, but it is more difficult to achieve the desired stable ethanol concentrations. The loading dose is 0.8 g/kg (4 mL/kg) of 20% (40 proof) ethanol diluted in juice administered orally or via a nasogastric tube(Howland, 2011).

6) MAINTENANCE DOSE

a) MAINTENANCE DOSE

1) Maintain a serum ethanol concentration of 100 to 150 mg/dL. Intravenous administration is preferred, but oral ethanol may be used if intravenous is unavailable(Howland, 2011; Barceloux et al, 2002).

INTRAVENOUS ADMINISTRATION OF 10% ETHANOL
Non-drinker to moderate drinker	80 to 130 mg/kg/hr (0.8 to 1.3 mL/kg/hr)
Chronic drinker	150 mg/kg/hr (1.5 mL/kg/hr)
ORAL ADMINISTRATION OF 20% (40 proof) ETHANOL*
Non-drinker to moderate drinker	80 to 130 mg/kg/hr (0.4 to 0.7 mL/kg/hr) orally or via nasogastric tube
Chronic drinker	150 mg/kg/hr (0.8 mL/kg/hr) orally or via nasogastric tube
*Diluted in juice

b) MAINTENANCE DOSE/ETHANOL DIALYSATE

1) During hemodialysis maintenance doses of ethanol should be increased in accordance with the recommendation given below, or ethanol should be added to the dialysate to achieve a concentration of 100 milligrams/deciliter (Pappas & Silverman, 1982).

c) MAINTENANCE DOSE/ETHANOL-FREE DIALYSATE

1) Maintain a serum ethanol concentration of 100 to 150 mg/dL(Howland, 2011; Barceloux et al, 2002):

INTRAVENOUS ADMINISTRATION OF 10% ETHANOL - 250 to 350 mg/kg/hr (2.5 to 3.5 mL/kg/hr)
ORAL ADMINISTRATION OF 20% (40 proof) ETHANOL* - 250 to 350 mg/kg/hr (1.3 to 1.8 mL/kg/hr) orally or via nasogastric tube
*Diluted in juice

2) Variations in blood flow rate and the ethanol extraction efficiency of the dialyzer will affect the dialysance(McCoy et al, 1979).
3) If the ethanol dialysance ((CL)D) is calculated, the infusion rate during dialysis (Kod) can be individually adjusted using the following expression (McCoy et al, 1979):

Kod = Vmax x   Cp   + (CL)D x Cp
             -------
             Km + Cp
where Cp = desired blood ethanol level
*  Vmax = 175 mg/kg/hr in chronic ethanol drinkers 
*  Vmax = 75 mg/kg/hr in non-chronic drinkers
*  Km = 13.8 mg/dL

7) PEDIATRIC DOSE

a) There is very little information on ethanol dosing in the pediatric patient (Barceloux et al, 2002). The loading dose and maintenance infusion should be the same as for an adult non-drinker. Loading dose is 0.8 g/kg (8 mL/kg) of 10% ethanol infused over 1 hour, maintenance dose is 80 mg/kg/hr (0.8 mL/kg/hr) of 10% ethanol (Howland, 2011).
b) Blood ethanol concentration should be initially monitored hourly and the infusion rate should be adjusted to obtain an ethanol concentration of 100 to 150 mg/dL (Howland, 2011; Barceloux et al, 2002).

1) Monitor blood glucose and mental status frequently during therapy (Howland, 2011). Ethanol-induced hypoglycemia is more common in children (Barceloux et al, 2002) and children may develop more significant CNS depression.

8) MONITORING PARAMETERS

a) ETHANOL CONCENTRATION

1) Blood ethanol concentrations should be determined every 1 to 2 hours until concentrations are maintained within the therapeutic range (100 - 150 mg/dL). Thereafter concentrations should be monitored every 2 to 4 hours. Any change in infusion rate will require monitoring every 1 to 2 hours until the therapeutic range is reached and maintained (Barceloux et al, 2002).

b) ADDITIONAL MONITORING

1) Monitor serum electrolytes and blood glucose, monitor for CNS depression (Howland, 2011).

9) DURATION OF THERAPY

a) SERUM CONCENTRATIONS AVAILABLE: Ethanol therapy should be continued until the following criteria are met:

1) Glycol ether blood concentration, measured by a reliable technique, is no longer detectable.
2) Glycol ether-induced acidosis (pH, blood gases), clinical findings (CNS, hyperventilation), electrolyte abnormalities (calcium, potassium), and osmolal gap have resolved.
3) NO SERUM CONCENTRATIONS AVAILABLE: Ethanol therapy should be continued for a minimum of 3 days in the absence of dialysis, one day when dialysis has been performed, or until clinical findings resolve, whichever is longer.
4) Endpoint of ethanol therapy for treatment of glycol ethers is arbitrary. Additional studies are needed to demonstrate efficacy and duration of therapy. Glycol ether serum concentrations are not routinely available and a toxic range has not been established.
5) If the clinical findings have not resolved it may indicate the continued presence of glycol ether, metabolites, or both or some other etiology.
6) Serum osmolality may not be indicative of exposure (Lund et al, 1983).

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

A)

1) Hemodialysis is indicated, if severe acidosis or renal failure is present. The value of early hemodialysis to remove the substance has not been examined, but may be beneficial following severe poisoning (HSDB , 2000).

Abstracts

Range Of Toxicity

Summary

A)

Maximum Tolerated Exposure

A)

B)

C)

D)

1) ORAL/NON-TOXIC: Rats consuming drinking water for 30 days containing 0.051 grams/kilogram/day developed no adverse effects (Smyth & Carpenter, 1948).
2) ORAL/TOXIC: Rats consuming drinking water for 30 days containing 0.094 and 0.65 grams/kilogram/day developed reduction in appetite and histopathologic injury in either the kidney, liver, spleen, or testes (Smyth & Carpenter, 1948).
3) INHALATION: Animal data indicate there is little hazard associated with a single vapor exposure in part because of its low vapor concentration (Clayton & Clayton, 1994).

Workplace Standards

A)

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Under Study

1) Diethylene glycol monobutyl ether

a) TLV:

1) TLV-TWA:
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: Not Listed
2) Codes: Not Listed
3) Definitions: Not Listed

c) TLV Basis - Critical Effect(s):
d) Molecular Weight:

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS112-34-5 (National Institute for Occupational Safety and Health, 2007):

1) Not Listed

C) Carcinogenicity Ratings for CAS112-34-5 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed ; Listed as: Diethylene glycol monobutyl ether
2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS112-34-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Not Listed

Toxicity Information

7.7.1)

A) LD50- (INTRAPERITONEAL)MOUSE:

1) 850 mg/kg ((RTECS, 2000))

B) LD50- (ORAL)RAT:

1) 5.66 g/kg ((RTECS, 2000))
2) 6.56 g/kg ((RTECS, 2000))

Pharmacology Toxicology

Physicochemical

Physical Characteristics

A)

Molecular Weight

A)

Other

A)

1) Currently not available (CHRIS , 2002)

Animal Toxicology

References

General Bibliography

1)

2)

3)

4)

5)

6)

7)

8)

9)

10)

11)

12)

13)

14)

15)

16)

17)

18)

19)

20)

21)

22)

23)

24)

25)

26)

27)

28)

29)

30)

31)

32)

33)

34)

35)

36)

37)

38)

39)

40)

41)

42)

43)

44)

45)

46)

47)

48)

49)

50)

51)

52)

53)

54)

55)

56)

57)

58)

59)

60)

61)

62)

63)

64)

65)

66)

67)

68)

69)

70)

71)

72)

73)

74)

75)

76)

77)

78)

79)

80)

81)

82)

83)

84)

85)

86)

87)

88)

89)

90)

91)

92)

93)

94)

95)

96)

97)

98)

99)

100)

101)

102)

103)

104)

105)

106)

107)

108)

109)

110)

111)

112)

113)

114)

115)

116)

117)

118)

119)

120)

121)

122)

123)

124)

125)

126)

127)

128)

129)

130)

131)

132)

133)

134)

135)

136)

137)

138)

139)

140)

141)

142)

143)

144)

145)

146)

147)

148)

149)

150)

151)

152)

153)

154)

155)

156)

157)

158)

159)

160)

161)

162)

163)

164)

165)

166)

167)

168)

169)

170)

171)

172)

173)

174)

175)

176)

177)

178)

179)

180)

181)

182)

183)

184)

185)

186)

187)

188)

189)

190)

191)

192)

193)

194)

195)

196)

FeedBack

BUTOXYETHOXY ETHANOL

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Vital Signs

Heent

Respiratory

Genitourinary

Acid-Base

Dermatologic

Reproductive

Carcinogenicity

Monitoring Parameters Levels

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Summary

Maximum Tolerated Exposure

Workplace Standards

Toxicity Information

Physical Characteristics

Molecular Weight

Other

General Bibliography